TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29641	89146;89147;89148	chr2:178554190;178554189;178554188	chr2:179418917;179418916;179418915
N2AB	28000	84223;84224;84225	chr2:178554190;178554189;178554188	chr2:179418917;179418916;179418915
N2A	27073	81442;81443;81444	chr2:178554190;178554189;178554188	chr2:179418917;179418916;179418915
N2B	20576	61951;61952;61953	chr2:178554190;178554189;178554188	chr2:179418917;179418916;179418915
Novex-1	20701	62326;62327;62328	chr2:178554190;178554189;178554188	chr2:179418917;179418916;179418915
Novex-2	20768	62527;62528;62529	chr2:178554190;178554189;178554188	chr2:179418917;179418916;179418915
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-104
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5037
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/K	rs772380405	0.103	0.122	N	0.235	0.166	0.269558022972	gnomAD-2.1.1	1.26E-05	None	None	None	None	N	None	0	9.09E-05	None	0	0	None	0	None	0	0	0
E/K	rs772380405	0.103	0.122	N	0.235	0.166	0.269558022972	gnomAD-4.0.0	2.75391E-06	None	None	None	None	N	None	0	6.92841E-05	None	0	0	None	0	0	9.02389E-07	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.1768	likely_benign	0.1867	benign	-0.66	Destabilizing	0.961	D	0.579	neutral	N	0.515555927	None	None	N
E/C	0.8285	likely_pathogenic	0.8271	pathogenic	-0.341	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
E/D	0.1587	likely_benign	0.1804	benign	-0.678	Destabilizing	0.961	D	0.541	neutral	N	0.467254181	None	None	N
E/F	0.7611	likely_pathogenic	0.7778	pathogenic	-0.164	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
E/G	0.2929	likely_benign	0.3235	benign	-0.956	Destabilizing	0.98	D	0.622	neutral	N	0.474179942	None	None	N
E/H	0.4549	ambiguous	0.482	ambiguous	-0.145	Destabilizing	0.996	D	0.627	neutral	None	None	None	None	N
E/I	0.3129	likely_benign	0.3199	benign	0.126	Stabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
E/K	0.1661	likely_benign	0.1881	benign	-0.137	Destabilizing	0.122	N	0.235	neutral	N	0.459430498	None	None	N
E/L	0.4173	ambiguous	0.4299	ambiguous	0.126	Stabilizing	0.97	D	0.66	neutral	None	None	None	None	N
E/M	0.4307	ambiguous	0.4454	ambiguous	0.295	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
E/N	0.283	likely_benign	0.3099	benign	-0.628	Destabilizing	0.985	D	0.559	neutral	None	None	None	None	N
E/P	0.9523	likely_pathogenic	0.9575	pathogenic	-0.115	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
E/Q	0.1414	likely_benign	0.1488	benign	-0.528	Destabilizing	0.489	N	0.397	neutral	N	0.48121128	None	None	N
E/R	0.2874	likely_benign	0.3141	benign	0.183	Stabilizing	0.942	D	0.532	neutral	None	None	None	None	N
E/S	0.2123	likely_benign	0.2302	benign	-0.837	Destabilizing	0.97	D	0.54	neutral	None	None	None	None	N
E/T	0.1934	likely_benign	0.1991	benign	-0.59	Destabilizing	0.985	D	0.606	neutral	None	None	None	None	N
E/V	0.1794	likely_benign	0.1815	benign	-0.115	Destabilizing	0.994	D	0.642	neutral	N	0.472015793	None	None	N
E/W	0.9164	likely_pathogenic	0.926	pathogenic	0.105	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Y	0.6602	likely_pathogenic	0.6867	pathogenic	0.098	Stabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.